We have solubilized 80-100 per cent of the particulate phosphodiesterase (PDE) with a combination of 30 mM Tris HC1, pH 8.0 mM, 3.0 mM MgSO4, 0.1 per cent Brij 30, 1 per cent Triton X-100, 5 mM DTT, 5 mM NaBr. The solubilized enzyme exhibits low Michaelis constants (ca. 0.6 micron M) for cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP). the increased activity of the particulate PDE produced by incubation of fat cells with insulin or ACTH is maintained in the solubilized state. The solubilized enzyme exhibits 2 peaks on PAGE electrophoresis (3.5 per cent gels) and DEAE chromatography. cAMP and cGMP PDE activity co-elute; the eluted material exhibit low Michaelis constants for cAMP and cGMP.